The aims of the study are to compare two dosing levels and the mode of administration of thyroid hormones or iodine supplementation in premature infants to achieve optimal plasma hormone targets. The health problem is that infants, have low thyroid hormones levels based on studies in which severe hypothyroxinemia is associated with an increased risk of Cerebral Palsy. Evidence suggests that a result from our trial will define the mode of therapy that improve long-term neurological outcomes .
Conditions
Interventions
Trade Name: Levothroid
Product Name: levothyroxine sodium T4
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Levothyroxine Sodium
Current Sponsor code: NDC# 55390-880-10
Other descrip
Sponsors
NINDS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The target population for this treatment is infants born prior to 28 completed weeks of gestation. All neonates admitted to the three clinical study sites (NY, Amsterdam, Madrid) will be screened for eligibility, regardless of ethnicity, race, nationality, religion, creed or gender. a. Patient Eligibility All neonates 24 0/7 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a) Absence of parental consent or assent of the treating physician b) A concurrent clinical trial with another randomized drug c) Other concern by treating physician that either mandates or prohibits study treatment d) Gestational age out of target range 24 0/7 weeks through 27 6/7 weeks. Eligibility only based on gestational age. No prior blood tests required. e) Death expected within 48 hours of birth due to severity of initial cardiopulmonary disease f) Mother of potential study subjects is a minor 5 contiguous days) f) Major congenital malformations requiring surgery i) Structural congenital heart disease (e.g. cyanotic heart defects) ii) Anomalies of the gastrointestinal tract (e.g. gastroschesis) g) Known chromosomal anomalies (e.g. Trisomy 21, 13 & 18) h) Neonatal cardiac arrhythmia’s causing output failure 4.2.3 Exclusions Based on Milk or Medications in Breast Milk a) Breast Milk i) Women taking anti-thyroid medications or supplemental iodine in therapeutic doses. ii) Issues of contraception are not applicable, as women do not typically receive these medications in the first 6 weeks post-partum. b) Formula Use of soy based formulas will be avoided since they are associated with prolonged increases in TSH even after treatment for congenital hypothyroidism. 4.2.4 Exclusions Based Upon Drug Exposures Since enrollment will be 1 ounce daily) or any use of heroin or methadone during the pregnancy are drugs that can interfere with thyroid hormone transport in serum51 b) Drugs that will NOT be cause for exclusion at enrollment: i) Common Drugs of Concern Include: -Dopamine, dobutamine & epinephrine drips: can cause TSH suppression. Dopamine will be tracked for use throughout the hospitalization but will not be cause for exclusion. -Steroid Use: Similar effects arise from the use of steroids as for dopamine. However, >90 % or all ELBW newborns are exposed to antepartum steroids during the pregnancy so it will not be a novel confounding factor. Use of antepartum steroids will be tracked along with achieved cortisol blood levels during the protocol. It will not be cause for exclusion. ii) Other Rarely Used Medications during Pregnancy: These substances are uncommonly used in the perinatal period and may affect thyroid status51 through effects on.: -Thyroid hormone metabolism: Phenobarbital -Displacement from protein
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): ;Main Objective: Primary Objective: The purpose of the pilot study is to establish the dosing schedules needed to achieve the optimal plasma hormone targets in the neonatal period, without increasing measures of neonatal morbidity, mortality or physiological dysfunction. Primary Hypothesis The central null hypothesis to be tested is that there is no difference in mean FT4 levels between any of the five treatment groups and the saline infusion placebo control group. ;Secondary Objective: a) A particular goal is to avoid suppression of thyroid stimulating hormone (TSH) due to administration of thyroid hormone and to determine its effects on endogenous cortisol levels. b) Does the iodine background contribute to variation in thyroid status and can iodine alone produce a euthyroid state in premature infants? Long Term Objectives a) We also aim to demonstrate cooperation among an international consortium of five participating institutions before initiating a trial to involve about 20 clinical study sites. c) The ultimate long-term goal of this Phase 1 pilot study is to set the stage for a large multicenter randomized trial. The long-term trial will test the hypothesis that thyroid hormone replacement therapy in preterm infants with transient hypothyroxinemia results in clinically significant improvement in cognitive functioning and reduction in the frequency of cerebral palsy. | — |
Countries
Spain
Outcome results
None listed